2022: Semaglutide for Obesity (Wegovy) (2022)

The FDA approval of high-dose semaglutide (Wegovy, 2.4 mg weekly subcutaneous injection, Novo
Nordisk) for chronic weight management in June 2021—with commercial launch in 2022—represented
the most effective pharmacological weight-loss treatment ever approved and catalysed a fundamental
reassessment of obesity as a treatable metabolic disease rather than a failure of willpower.
Semaglutide is a long-acting GLP-1 receptor agonist; at the higher 2.4 mg dose approved for
obesity, it achieved mean weight loss of approximately 15 % from baseline in the STEP 1 Phase III
trial—roughly three times the effect of previously available weight-loss medications and approaching
the outcomes achievable with bariatric surgery.

GLP-1 (glucagon-like peptide-1) is an incretin hormone secreted by L cells of the distal
intestine in response to nutrient ingestion; it acts centrally in the hypothalamus and brainstem
to reduce appetite and increase satiety, and peripherally to slow gastric emptying and augment
glucose-dependent insulin secretion. Semaglutide was originally developed and approved at lower
doses (0.5–1 mg weekly, branded Ozempic) for type 2 diabetes; its pronounced effect on body
weight at higher doses was characterised in the obesity development programme.

The SELECT cardiovascular outcomes trial, reported in 2023, demonstrated that semaglutide 2.4 mg
reduced major adverse cardiovascular events by 20 % in overweight or obese adults without diabetes
but with established cardiovascular disease—the first pharmacological weight-loss agent to show
hard cardiovascular outcome benefit, transforming the clinical positioning of GLP-1 agonists from
glycaemic agents to broad cardiometabolic medicines.

Global demand for semaglutide (and tirzepatide, the dual GLP-1/GIP agonist approved in 2023)
created unprecedented supply constraints and reshaped pharmaceutical market forecasts, with GLP-1
agonists projected to become the highest-revenue drug class in history.